Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis.
Bottom Line: Hence, we and others hypothesized that increasing telomerase expression by pharmaceutical compounds may protect brain cells from death caused by damaging agents.The survival of telomerase-expressing cells (i.e. motor neurons), but not telomerase-deficient cells, exposed to oxidative stress was increased by AGS-499 treatment, suggesting that the AGS-499 effects are telomerase-mediated.Therefore, a controlled and transient increase in telomerase expression and activity in the brain by AGS-499 may exert neuroprotective effects.
Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.Show MeSH
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Mentions: To directly examine the effect of the AGS compound on motor neuron survival after insult, we used the NSC-34 cell line, a common in vitro model for motor neuron-like cells (Matusica et al, 2008). Consistent with our previous results, the AGS compound increased telomerase expression and activity in these cells (Fig 9A, lanes 3 and 4, and Supporting information Fig 2A and B). NSC-34 cells were transfected with hTERT-GFP vector (NSC-34hTERT-GFP; Fig 9A, lane 1) and two TERT shRNA vectors (NSC-34shRNA69, NSC-34shRNA72), which reduced TERT expression and activity. NSC-34shRNA69 exhibited a 73% decrease in TERT expression, while NSC-34shRNA72 exhibited a 54% decrease (Fig 9A, lanes 5 and 7, and Supporting information Fig 2C). AGS treatment did not increase TERT expression in the shRNA-transfected cells but increased the expression of the endogenous TERT in NSC-34hTERT-GFP cells (Fig 9A).
Affiliation: The Shraga Segal Department of Immunology and Microbiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.